Accelerated partial breast irradiation with shielded brachytherapy applicator system and method of use

ABSTRACT

The system and methods of the invention partially shields the radiation dose to the skin and/or other anatomical organs by using magnetically responsive material that blocks radiation, which may be fine grains of iron or other ferrous powder for example. The powder is typically injected into an IB applicator, along with inflating saline solution in case of MSB, when a skin spacing problem is encountered, or there is a risk of high doses being delivered to the critical organs surrounding a lumpectomy cavity, for example. A slight magnetic field of predetermined configuration will be applied externally to arrange the shielding material internally under the segment of surface of the IB applicator where the skin spacing is typically less than 7 mm, thereby protecting the skin from radiation damage. Monte Carlo studies to develop parameterizations for treatment planning with the IB applicator utilizing the suggested shielding material is also provided.

This application is a continuation application of co-pending U.S.Non-Provisional patent application Ser. No. 11/905,719 filed on Oct. 3,2007, claims benefit of U.S. Provisional Application No. 60/849,020filed on Oct. 4, 2006, entitled “Accelerated Partial Breast Irradiationwith Shielded MammoSite Applicator and Method of Use,” the disclosuresof which are incorporated by reference herein in their entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention is directed to a device and method for providing radiationtherapy, and more specifically, a device, system and method forproviding shielded intracavitary brachytherapy (IB).

2. Related Art

For years, women with early stage breast cancers have had the option tochoose breast conserving therapies (BCTs) over mastectomy. About 130,000women are candidates for BCT in the U.S. annually. Until the mid 1990's,the only available BCT was lumpectomy, followed by external beamradiation therapy (EBRT) delivered to the whole breast in daily dosesfor 5-7 weeks. The combination of lumpectomy and EBRT has proven to beeffective in preventing local recurrence of tumor. Despite BCT's successin fighting cancer, issues associated with scheduling 5-7 weeks of EBRThave prevented many from taking advantage of BCT. In some areas of thecountry, as few as 10% of medically eligible patients receive BCT.Moreover, whole breast irradiation is considered a significantcontributor to adverse effects associated with this form of BCT.

Recently, methods for accelerated partial breast irradiation (APBI) havebeen developed, such as the technology for intracavitary brachytherapy(IB) of the breast marketed, for example, by Hologic, Inc., CiannaMedical, Xoft, Inc., and/or SenoRx, Inc. These allow patients tocomplete radiation treatment in 5 days. These also have better confinedirradiation margins. The minimally invasive MammoSite Radiation TherapySystem (MRTS) (such as marketed by Hologic, Inc.) appears to be the mostwidely used and fastest growing form of APBI.

MRTS works generally by implanting a small balloon into the cavityremaining after tumor removal. The balloon is inflated within the breastand then loaded with a tiny radioactive seed to deliver radiation frominside the breast directly to the tissue where cancer is most likely torecur, as well as farther from the skin where adverse reactions andcosmetic damage are dominant considerations.

If the skin-to-balloon distance is less then 7 mm, patients are not ableto take advantage of MRTS. Studies show that this may affect as many as4,000 patients each year. Small skin-to-balloon distances are associatedwith mild to acute adverse skin reactions, as in previous external beamtherapies. These significantly impact the cosmetic outcome of BCT, whichis a crucial consideration for patients undergoing breast preservingtreatment.

Breast Conserving Therapy

Outcomes of multiple retrospective studies and randomized prospectivetrials have consistently demonstrated no significant differences betweenBCT and mastectomy in disease-free survival, distant disease-freesurvival and overall survival for an appropriately selected patientpopulation. BCT typically involves breast-conserving surgery andradiotherapy. Until the mid 1990's the radiation therapy associated withBCT usually involved 5-7 weeks of daily treatment with external beamradiation delivered to the whole breast (during the last two-weeks oftreatment a boost dose of radiation was typically delivered only to thetumor bed). The biologic argument for whole breast irradiation comesfrom various studies demonstrating that breast cancer is oftenmulticentric.

Studies demonstrate that the logistic and temporal problems ofscheduling 5-7 weeks of external beam radiation therapy (EBRT) have asubstantial effect on patient's choice of treatment. As a result, incertain parts of the United States, as few as 10% of medically eligiblepatients receive BCT. Thus, even though breast-conserving surgery andEBRT have been proven to be equivalent to mastectomy in the managementof women with early-stage breast carcinoma, this form of BCT has limitedpracticality. Additionally, it has not been definitively established howmuch of the clinically uninvolved breast tissue surrounding thelumpectomy cavity must be treated by radiation. Treatment of clinicallyuninvolved breast tissue with EBRT after lumpectomy is generallybelieved to play a significant role in the occurrence of acute andchronic toxicity associated with this form of BCT. Moreover, largeretrospective reviews have shown that, in certain subsets of patientswith early-stage breast cancer, incidence of failures outside thelumpectomy bed are rare, and the use of whole breast EBRT does notappear to significantly affect the incidence of failure outside thetumor bed.

In the face of these shortcomings of whole-breast EBRT, investigationswere initiated to develop treatments that limit radiation treatment tothe surgical bed plus a 10-20 mm margin of tissue circumferentially forthe management of patients with early stage breast cancers whoadditionally satisfied certain medical eligibility criteria. Rationalefor the new methodology also emphasized the delivery of larger doses ofradiation per fraction to the lumpectomy cavity. This acceleratedpartial breast irradiation (APBI) therapy aims to preserve local controland cosmesis while decreasing the overall length of the treatment, andis typically completed for APBI in 5-7 days. The objective is to providethe breast conserving option to a larger population of women throughoffering a new method that is logistically simpler and more practical,and in prospective has reduced treatment related toxicities. APBItherapy addresses problems that are both side-effect and quality of liferelated.

Interstitial and Intracavitary APBI

Multicatheter-based interstitial brachytherapy was the focus of initialstudies evaluating APBI therapy. It was used to treat the excision siteplus an additional 10-20 mm margin of tissue. Follow-up data at a medianof 6 years suggest that multicatheter-based APBI is comparable towhole-breast irradiation in both safety and efficacy. Despiteencouraging clinical results, only a minority of institutions haveadopted multicatheter-based interstitial brachytherapy. Apparentlybecause the optimal outcome of the treatment requires extensivepractitioner experience associated with both the complexity of theprocedure and with the associated intricate and time-consuming treatmentplanning.

The MammoSite brachytherapy (MSB) applicator is one example of a new andpotentially superior technology for APBI therapy, which is intended todeliver intracavitary radiation to the surgical margins afterlumpectomy. The device is a double lumen balloon catheter that issurgically inserted into the tumor bed during a lumpectomy procedure orpostlumpectomy during a separate open or ultrasonically guided closedprocedure within ˜10 weeks of the surgery.

The balloon catheter is inflated with a saline/contrast mixture to fillthe entire cavity. Conformance to the surrounding tissue is checkedusually with a computed tomography (CT) scan. CT images are also used toensure an absence of air pockets between the balloon and the surroundingtissue, as well as to measure the balloon diameter, symmetry, andproximity to the skin and chest wall. The balloon catheter may be usedas a high-dose rate (HDR) brachytherapy applicator to deliverintracavitary highly conformal radiation to the surgical margins plustypically an additional 10 mm of tissue surrounding the tumor bed toinclude clinically unapparent microscopic disease beyond the resectionmargins.

The MSB applicator simplifies delivery of HDR breast brachytherapy.First Phase I and II trials have already demonstrated that the deviceperforms well clinically and provides improved dose coverage andreproducibility compared to interstitial implantation, as well as beingeasy to implant.

Success and Limitations of MSB

Eighty-seven institutions and 1,419 patients with stage 0, I, or IIbreast carcinoma who were undergoing breast conserving therapy wereenrolled in a trial designed to collect data on the clinical use of theMammoSite breast brachytherapy catheter for delivering breastirradiation from May 4, 2002 through Jul. 30, 2004. The MSB device wasplaced in 1,403 of these patients. The MSB catheter demonstratedacceptable technical reproducibility between multiple institutions anduse in appropriate groups of patients in delivering APBI. Cosmeticresults at 12 months (92% good/excellent) were comparable to thosereported for whole-breast radiation therapy. Early toxicity rates(infections, radiation recall) appeared acceptable. The recommendedradiation dose fractionation scheme was 34 Gray (Gy) delivered at apoint 10 mm from the surface of the balloon in 3.4 Gy fractions (twicedaily separated by a minimum of 6 hrs) over 5 to 7 elapsed days withvarious commercially available, remote HDR after-loaders.

Skin Spacing—Correlation to Cosmesis:

The results of the MSB catheter trial described above confirmed previousobservations that early cosmesis is related strongly to skin spacing. At12 months, 96% of patients had a good/excellent cosmetic result withskin spacing ≧7 mm. 86% of patients with <7 mm of skin spacing had agood/excellent cosmetic result, suggesting that other factors(area/volume of tissue receiving higher doses) may impact on theultimate cosmetic result. In 12% of patients with <7 mm of skin spacing,significant radiation effects were readily observable, and 2% had severesequalae of breast tissue secondary to radiation effects. One of thetechnical eligibility criteria for participation in this trial wasminimum applicator-to-skin distance of 5 mm. Explantation of the devicedue to inadequate balloon-to-skin distance was an overwhelming 35% ofall explanted patients (3.1% overall).

Another recent study has analyzed factors associated with the cosmeticoutcome achieved using the MSB applicator to treat patients with partialbreast irradiation. The study population comprised 30 patients. 53.3% ofthe patients were reported to have an excellent cosmetic outcome and 40%had a good cosmetic outcome. The mean maximal skin doses per fraction inthe excellent and good outcome groups were 354.8 cGy and 422.3 cGy,respectively. Excellent cosmetic outcome was also associated with agreater balloon-to-skin distance.

Approximately 130,000 women are candidates for BCT in the United Stateseach year. Since the MSB treatment system's FDA approval in 2002, over22,000 patients have been treated with this procedure. It has again beennoted that the skin-balloon surface distance and balloon-cavityconformance were the main factors limiting the initial use of theMammoSite applicator. As the use of the MSB treatment system grows, itis estimated that this limitation may effect as many as 4,000 patientseach year.

Radiation Recall Reactions—Skin Spacing, Chemotherapy:

Radiation recall reaction is usually broadly referring to thegeneralized development of a significant skin reaction (erythema,dry/moist desquamation) approximately 37 weeks after the completion ofradiation therapy. Thus, both a delayed effect of radiation therapy onthe skin and a redevelopment of a skin reaction secondary to theadministration of radiosensitizing drugs are referred to as radiationrecall reactions. It is believed that this effect is enhanced by theconcurrent use of certain systemic chemotherapy agents. Adriamycinradiation recall dermatitis has been associated with external beamradiation therapy for 30 years, for example.

Development of a radiation recall reaction was evaluated in the RegistryTrial on clinical use of the MSB described above, and of 442 patientsthat were evaluated for radiation recall reaction, 74 of these patientshad received chemotherapy. A recall reaction was developed in 13.5% ofpatients who received chemotherapy (10 patients) versus only 1.4% (5patients) who did not receive chemotherapy. Thus, patients who receivedconcurrent chemotherapy were more likely to experience a recallreaction, suggesting that, in some patients, the early use of systemicchemotherapy agents can exacerbate or precipitate this reaction. Out ofthe 15 patients who developed a recall reaction, 3 had skin spacing <7mm (6% of 50 patients with <7 mm skin spacing) versus 12 of 392 patients(3%) who had skin spacing >7 mm. Thus, again, patients with smaller skinspacing more frequently experienced a recall reaction (withoutchemotherapy).

If future studies confirm with higher certainty the association ofradiation recall reaction after APBI therapy with adjuvant chemotherapy,some precautions will need to be considered. These safety measures mayinclude 1) the delayed start of chemotherapy, 2) avoidance of certainradiosensitizing drugs, or 3) use only in patients with greater skinspacing.

Clinical Target Volume and MSB:

As already mentioned, the precise amount of clinically uninvolved tissuethat must be included within the high-dose volume has not yet beendefinitively established. During multicatheter interstitialbrachytherapy the amount of uninvolved tissue treated is an additional10-20 mm circumferentially to the lumpectomy cavity. Three-dimensionalconformal radiation therapy (3DCRT) is a relatively new and lessinvasive form of APBI. 3DCRT employs multiple noncoplanar beams toprovide a relatively more focused dose of radiation to the excision citeplus, again, a 10-20 mm margin.

Earlier studies with the MSB applicator have included up to anadditional 15 mm of tissue circumferentially. However, therapy protocolsthat are currently used in everyday practice include only 10 mm ofclinically uninvolved tissue. Limiting factors potentially include thedose to portions of the heart and lung, but the principal dose-limitingfactor for MSB is the dose to the overlying skin. Thus, a majorconsideration for a somewhat reduced size of the circumferentiallytreated tissue during MSB is not yet established clinically orscientifically, but is dictated by risk management of significant skinreactions. Yet, some studies have documented microscopic spread beyond20 mm from the edge of the gross tumors in 29% of women with extensiveintraductal component-negative breast cancers.

Improvements to the above procedures would increase overall effectivetreatment.

SUMMARY OF THE INVENTION

The various features of the invention improves radiation therapy overalland in certain situations, provides a simple yet effective method ofminimizing these problems above, thereby both making BCT available to alarger population of women, as well as cosmetically more favorable toall, and improved radiation treatment delivery in general. In oneaspect, a method partially shields the radiation dose to the skin byinjecting fine grains of shielding powder into the balloon during theprocedure with MRTS when a skin spacing problem is encountered. A slightexternal magnetic field is applied and, as the powder aligns to thisfield, a thin layer of radiation protection for the skin (or othertissue to be protected) will be formed. Full clinical realization ispossible, including treatment planning.

In one aspect among many, the innovation to the MRTS allows more womento take advantage of APBI and therefore also of BCT. Moreover, thisimproved technology development facilitates better cosmetic outcome forall APBI patients, especially those also undergoing adjuvantchemotherapy.

In another aspect, a method of brachytherapy is provided. The stepsinclude creating a radiation shield in a subject by applying a magneticfield to attract shielding material to dynamically form the radiationshield against a surface of an enclosure and applying a radiation dosewherein the radiation dose is blocked at least in part by the formedradiation shield so that radiation dose is deliverable to one area ofthe subject and is at least partially blocked to another area of thesubject.

In yet another aspect of the invention, a method of brachytherapy isprovided that includes the steps of inserting an applicator into asubject, the applicator configured to receive shielding material and aradiation source, placing the shielding material and a radiation sourcein the applicator and applying a magnetic field to align the shieldingmaterial along a surface of the applicator to shield a tissue arearequiring protection from radiation emitted by the radiation source.

In still another aspect of the invention, a system for radiationtreatment is provided that includes an applicator having a flexiblecontainment portion configured to receive a radiation source andunformed radiation shielding material and a magnetic source configuredto dynamically form a radiation shield by generating a magnetic fieldcausing the unformed shielding material to be spatially formed by themagnetic field along a surface of the flexible containment portion,wherein radiation emitted by the radiation source is blocked in part bythe formed radiation shield to protect a tissue area not under radiationtreatment.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide a furtherunderstanding of the invention, are incorporated in and constitute apart of this specification, illustrate embodiments of the invention andtogether with the detailed description serve to explain the principlesof the invention. No attempt is made to show structural details of theinvention in more detail than may be necessary for a fundamentalunderstanding of the invention and the various ways in which it may bepracticed. In the drawings:

FIG. 1 is a functional block diagram to illustrate a system according toprinciples of the invention while in use to provide shielding at aradiation treatment site;

FIG. 2 is an exemplary illustration showing how a magnetic fieldcontrols shielding material in a variable type balloon, according toprinciples of the invention;

FIGS. 3A and 3B are exemplary illustrations showing possible generalorientation and some affects of the system of the invention;

FIG. 4A is a flow diagram of an embodiment showing steps of shieldingradiation at a treatment site, according to principles of the invention;

FIG. 4B is a flow diagram showing exemplary steps of an overalltreatment process, according to principles of the invention; and

FIG. 5 is a flow diagram showing steps for modeling various factorsrelated to the optimizing dose distribution, according to principles ofthe invention.

DETAILED DESCRIPTION OF THE INVENTION

The embodiments of the invention and the various features andadvantageous details thereof are explained more fully with reference tothe non-limiting embodiments and examples that are described and/orillustrated in the accompanying drawings and detailed in the followingdescription. It should be noted that the features illustrated in thedrawings are not necessarily drawn to scale, and features of oneembodiment may be employed with other embodiments as the skilled artisanwould recognize, even if not explicitly stated herein. Descriptions ofwell-known components and processing techniques may be omitted so as tonot unnecessarily obscure the embodiments of the invention. The examplesused herein are intended merely to facilitate an understanding of waysin which the invention may be practiced and to further enable those ofskill in the art to practice the embodiments of the invention.Accordingly, the examples and embodiments herein should not be construedas limiting the scope of the invention, which is defined solely by theappended claims and applicable law. Moreover, it is noted that likereference numerals represent similar parts throughout the several viewsof the drawings.

It is understood that the invention is not limited to the particularmethodology, protocols, devices, apparatus, materials, applications,etc., described herein, as these may vary. It is also to be understoodthat the terminology used herein is used for the purpose of describingparticular embodiments only, and is not intended to limit the scope ofthe invention. It must be noted that as used herein and in the appendedclaims, the singular forms “a,” “an,” and “the” include plural referenceunless the context clearly dictates otherwise.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art to which this invention belongs. Preferred methods, devices,and materials are described, although any methods and materials similaror equivalent to those described herein can be used in the practice ortesting of the invention.

There is a strong correlation between the cosmetic outcome of treatmentof women or other subjects with early-stage breast cancer utilizing thewell known MammoSite brachytherapy applicator and the spacing betweenthe MammoSite balloon surface and the skin. Many women are not able totake advantage of MSB because of inadequate balloon-to-skin distances.Additionally, a large Registry Trial involving eighty seven institutionsas well as some Phase II trials indicate that there is a definitecorrelation between radiation recall reactions and chemotherapy whenadministered within several weeks of external beam radiation therapy ofthe whole breast or partial breast irradiation therapy. Radiation recallreactions appeared more often if the skin dose per fraction was higherdue to smaller skin spacing. Furthermore, some studies show that it maybe required to increase clinical target volume margins beyond 10 mm,which is the standard in current clinical practice with MammoSite.However, the implementation of a thin, customizable, shielding layer tothe MammoSite procedure significantly reduces all of these concerns,thereby facilitating increased access to the procedure, improvedcosmetic outcome, and reduced radiation recall reactions.

Reference herein is made primarily in view of MRTS because of its widespread use and the availability of clinical data. However, it should benoted that the various improvements to the method of intracavitarybrachytherapy (IB) delivery are directly applicable to all of the IBtreatment methods of the breast, and any other body parts where thinlayer radiation shielding may be warranted. Therefore, it should beunderstood that other body parts of a subject (i.e., human or non-humansubject) may benefit as well by the treatment technique describedherein.

The various aspects of the invention provide several advantages overprior known technology including, but not limited to:

1) a practical way of reducing skin dose during the intracavitarybrachytherapy of the breast via the use of shielding materials in amagnetic field for shielding part of the internal surface of the IBapplicator, using optimal shielding powder configuration, material andamount. Similarly, the required electromagnetic field strength andconfiguration for shield shaping is provided by the invention.

2) an analytic model based on precision Monte Carlo simulations andlaboratory data for determination of the required amount of powders tolimit the skin dose to an optimal value deduced from several clinicaltrials.

3) a method and technology for application and measurement of a magneticfield which is both practical and reproducible, and provides the desiredspatial distribution of shielding powders in the IB applicator.

4) a treatment planning algorithm for the IB procedure that takes as aninput the analytic model and which may easily be incorporated into anexisting brachytherapy treatment planning program for IB.

5) steps for implementing an entire procedure including treatmentplanning, powder insertion in balloon in phantom, magnetic fieldapplication external to phantom, and resulting dose measurement.

Shielded Intracavitary Brachytherapy Applicator

As described previously, prior to the invention, the risk of high dosesto the skin overlying the balloon during the MSB procedure leads to anumber of limitations and results in certain deficiencies associatedwith this treatment. It is, therefore, most desirable to mitigate suchlimitations by use of a technique and/or system to reduce the dose tothe skin overlying and anatomical organs surrounding the IB applicatorballoon while maintaining the prescribed dose to the tissue surroundingthe tumor bed. A solution is provided by the methods and system of theinvention, which improve cosmetic outcome after IB therapy, such as MSBtherapy; reduce the risk of radiation recall reactions when patients aretreated with IB and adjuvant systemic chemotherapy; allow increase inclinical target volume margins beyond 10 mm if proven necessary; andallow a larger population of women to take advantage of the breastconserving IB treatment who otherwise were ineligible due to inadequateIB applicator-to-skin distances.

FIG. 1 is a functional block diagram to illustrate a system according toprinciples of the invention while in use to provide shielding at aradiation treatment site, generally denoted by reference numeral 100. Inthe example of FIG. 1, breast 103 is representatively shown as having atreatment site 105, which might be a tumorous area within breast 103,and is shown being treated with radiation using the system 100,described below, and also is shown as having portions of breast 103being shielded from radiation during treatment by system 100, such asthe tissue near and including the areola 150 area. Breast area denotedby reference numeral 155 illustratively represents breast tissue deeperwithin the breast 103 which may be adjacent at least in part to theintended treatment site 105. Although shown in FIG. 1 in two dimensionsfor simplicity, these breast portions, i.e., treatment site 105 andtissue 155, typically involve three dimensions.

The system 100 typically includes an applicator such as catheter 110,perhaps a multilumen silicon catheter, having a radiation source pathwayinteriorly formed along its length with a variable inflation balloonportion 120. Further included in the system is a radiation source 125(e.g., a ¹⁹²Ir radiation seed) that might be delivered by an afterloader115 (typically a high dose rate afterloader) having a delivery mechanism117 to the catheter 110 for delivering a radiation dose to the treatmentsite 105.

FIG. 1 further illustrates that the catheter 110 with balloon portion120 has already been advanced to the treatment site 105 through theincision 130. The balloon portion 120 is shown as having already beeninflated by a solution, typically a saline solution, via fluid injectionsite 145. The system 100 also includes shielding material 140 and amagnet source 135 that can be applied to direct the placement andspatial orientation of the shielding material 140 within balloon portion120. The shielding material 140 may comprise iron powder or anothersuitable magnetically susceptible material that provides radiationshielding ability. In the example of FIG. 1, under influence of amagnetic field, the orientation of the shielding material 140 is shownas creating a radiation shield along the inner surface of balloonportion 120 between the radiation source 125 and the skin layer proximalto the areola 150 area of the breast 103. Any tissue between theshielding material 140 (i.e., the shield) and the skin layer proximal tothe areola 150 would also be shielded.

The spatial orientation of the shielding material 140 along the innersurface of the balloon portion 120 may be controlled by varying theposition of the externally applied magnetic source 135 and/or varyingthe magnetic field intensity produced by the magnetic source 135. Thisvarying might include changing the electromagnetic characteristics, ifthe magnetic source is an electromagnet; or, if the magnetic source is apermanent type magnet, changing or selecting a magnet of a particularstrength, physical size and/or physical configuration.

If warranted based on a treatment plan, a broader shielding area (or,conversely, less broad shielding area) could be achieved by using more(or less) shielding material 140 and configuring the magnet 135 tospread the shielding material 140 in a broader (or less broad)configuration. Depending on the requirements of a treatment goal, a verysubstantial portion of the inner surface of the balloon portion 120could be shielded as necessary with an appropriately configured andapplied magnetic source 135 and adequate amount of shielding material140. Furthermore, the magnetic field may be managed to provide ashielding area that has nearly any configuration and not simplysubstantially oval or substantially circular shapes, but irregularshapes as well.

The possibly fine grains of shielding material, such as iron, may beused to partially shield radiation to the skin (or other selectedtissue) overlaying the IB applicator balloon, or similar applicator.Iron is used as an example material here, as it is both ferrous and awell known shield against photons for wide range of energies. Othermaterials, some composites, have similar properties and could beutilized equally well. These grains both respond well to appliedmagnetic fields and also move to a controllable configuration in themagnetic field. The shielding material blocks radiation at leastpartially. In some embodiments, the shielding material may be in theform of platelets. In some instances, the shielding material maycomprise magnetically susceptible steel alloy.

FIG. 2 is an exemplary illustration showing how a magnetic fieldcontrols shielding material in a variable type balloon 210, according toprinciples of the invention, generally denoted by reference numeral 200.Magnetic source 205 can be managed to distort the balloon 210 somewhat(but distortion of the balloon is not a necessary effect) by attractionof the shielding material 215 within the variable type balloon 210. Theex vivo exemplary balloon 210 is representative of the types of ballooncharacteristics and effects that could be employed with a catheter orsimilar applicator for in vivo applications, such as discussedpreviously in relation to the balloon portion 120. The spatialconfiguration of the shielding powder 215 is also controllable by theintensity and/or shape of the magnetic field generated by the magneticsource 205. Resulting shapes may be substantially oval, substantiallycircular, substantially linear, substantially rectangular, or evenirregular.

In addition to iron, other shielding materials having magneticsusceptibility are possible. These might include and are not limited togold-iron alloys with different concentrations of iron, and iron oxidenanoparticles and microparticles, for example. In these other shieldingmaterials that may be in powder form, both reduced toxicity concerns (incase of balloon breakage) and also greater magnetic susceptibility mayplay a role as relevant factors when deciding on a type of shieldingpowder for a particular application.

FIGS. 3A and 3B are exemplary illustrations showing possible generalorientation and some affects of the system of the invention. In FIG. 3A,a body part 310 is under radiation treatment. An enclosure 315 (invivo), which might be the balloon portion of a Mammosite catheter, forexample, encloses radiation shielding material 312, perhaps iron powder,for example. Within enclosure 315 a radiation source 320 is shown. Apermanent magnet 305 a and its magnetic field 307 (typically ex vivo)are shown attracting the radiation shielding material 312 to form ashield along the inner surface of the enclosure 315. The shield (i.e.,radiation shielding material 312) is shown as blocking a portion of theradiation (denoted by reference numeral 325) while other portions of theradiation are not blocked (denoted by reference numeral 330). In thisexample, the skin layer and neighboring tissue (which typically includesthe tissue area between the shield 312 and the magnet 305 a), designatedgenerally by reference numeral 340, are protected from the full effectsof the radiation source 320, while the treatment area within body part310 receives an intended radiation dose. The size and shape of theradiation shielding material 312 is related to the magnetic fields 307produced by the permanent magnet 305 a.

Referring now to FIG. 3B, the same situation is found as in FIG. 3Aexcept that the magnet 305 b is a controllable electromagnet (i.e., themagnetic fields are controllable) and the size of the radiationshielding material 312 along the inner surface of the balloon is largerdue to a wider and perhaps stronger magnetic field 307, as compared withFIG. 3A. Also, an applicator 335 is now shown delivering the radiationsource 320 to the treatment site in the body part 310 and for inflatingballoon 315. Again the skin layer and neighboring tissue, designatedgenerally by reference numeral 340, are protected from full radiationexposure emanating from radiation source 320. In both FIGS. 3A and 3B,the placement of the magnet is typically a matter of the treatment plan,usually developed at least in part using a modeling tool, discussedbelow.

FIG. 4A is a flow diagram of an embodiment showing steps of shieldingradiation at a treatment site, according to principles of the invention,starting at step 400. The steps of FIG. 4A may be used in conjunctionwith the system of FIG. 1, for example. At step 405, an applicator suchas a catheter is inserted into a subject for placement of the IBapplicator balloon portion proximate to the treatment site. At step 410,the shielding material (such as shielding material 140) is typicallyinjected into an IB applicator balloon, usually in those cases when askin spacing situation is encountered. In case of the MRTS, theshielding material may be injected along with an inflating salinesolution (for inflating the balloon). Prior to applying a magneticfield, the shielding powder is generally considered “unformed.”

At step 415, the shielding powder may be spatially rearranged under thesurface of the balloon (i.e., against the inner surface of the balloon120) underlying the skin or overlaying an anatomical organ byapplication of a relatively small magnetic field external (i.e.,usually, but not necessarily external) to the skin. The applied magneticfield causes the shielding powder to dynamically create an expandedshielding surface (typically a rather thin layer) based on the shape anddirectionality of the applied magnetic field (creating a “formed”shield). The shape of the expanded shielding surface may be varied byaltering the intensity and/or directionality of the applied magneticfield. In this way a shielding “umbrella” of a size and shapeappropriate to the treatment circumstance may be created by configuringthe shielding powder with a desired spatial orientation, typically inopposition, at least in part, to the radiation source being applied(step 420). This “umbrella” blocks and/or reduces the radiation dose tothe skin and/or any anatomical organs or tissue that may be desirable toexclude or limit from radiation treatment. The process ends at step 425.

In parallel, or typically prior to therapy, Monte Carlo simulation maybe performed to determine the necessary amount of shielding powder forlimiting the dose to the skin and/or anatomical organs (or tissue) notunder treatment. The dose limits that result in excellent/good cosmeticoutcomes can be inferred from the available clinical trial data (approx.350-450 cGy). Different balloon-to-skin distance scenarios may also besimulated. The results of the simulation may be tested in a laboratoryusing breast phantoms implanted with an IB applicator. The radiationdose delivered to the surface of the breast may be verified frommeasurements with a detector such as a MOSFET detector, which has beenproven to be a very effective radiotherapy surface dose detector. TheMOSFET detector has also been tested with good results for a ¹⁹²Irsource (e.g., a ¹⁹²Ir radiation seed), typically employed in MSBprocedures. Alternatively, an external functional imager, such as agamma camera, can be utilized to monitor both dose and position. Forposition of shielding material and catheter alone, an external x-ray orCT image could be obtained. Using combined laboratory and Monte Carlosimulation data, an analytical model for surface dose calculation may beproduced that is acceptable for treatment planning.

In one aspect, the model provides the required thickness of theshielding powders to achieve the desired dose limits at the skin (orother tissue) for a given skin-to-balloon distance and balloon size orgeometry. It is possible to specify both skin-to-balloon distance andthe skin dose limit as input parameters to the model. In another aspect,the model predicts the necessary magnetic field strength, shape anddistance from the IB applicator for shielding shaping. The modelincludes the dependence of all of these parameters on the shieldingpowder's magnetic susceptibility. A range of magnetic field strengthsthat are adequate for a range of shielding powder layer thicknesses thatare likely to be used in the clinic are determined. Magnetic fieldstrength from the higher end of this range is typically used inpractice.

Magnetic field configurations also provide optimal and reproducibleshielding material spatial distributions under the surface of the IBapplicator balloon. Commercially available magnetic field generators andmagnetic field measurement devices may be used, perhaps customized.Electromagnets may also be used. This allows for dynamic varying ofmagnetic field characteristics, such as field shape, strength anddistance from the IB applicator balloon. Measurement of the magneticfield(s) is practical and reproducible and provides a basis for shapingthe spatial distribution of the shielding materials.

The methods and system of the invention includes providing optimalcombination of magnetic field parameters and different shieldingpowders. Permanent magnets and electromagnets may be employed. Widevariety of customizable permanent magnets of various flexible shapes andstrengths are commercially available, and may be quite suitable forcontrolling relevant parts of the treatment. Test results show that arelatively slight magnetic field is needed to accomplish formation ofthe shielding powder configuration (not much stronger than a commonlyknown strong “refrigerator magnet”). However, stronger magnets may beused, as appropriate.

Since CT images are typically used for treatment planning for MSB, apotential problem of CT metal artifacts from shielding powders is alsoaddressed. An approach to reducing CT metal artifacts in intracavitarybrachytherapy using acquired raw projection data, enables an algorithmthat determines separate contributions from metal and non-metal objects.Images reconstructed using such algorithms contain no metal artifacts.

FIG. 4B is a flow diagram showing exemplary steps of an overalltreatment process, according to principles of the invention, starting atstep 450. At step 455, an applicator, such as a catheter (e.g., aMammoSite catheter) may be implanted in the subject's body part andlocalized proximate to a treatment site for radiation therapy. Theballoon portion may also be inflated. At step 460, an image may be takenof the body part to verify the actual distance and placement of theapplicator balloon in relation to the treatment site and/or surfacelayer (e.g., skin layer) and altering, as deemed necessary. At step 465,a check is made to determine if shielding is warranted based on apredetermined distance threshold of the distance from the balloon to thesurface layer and/or distance from the anticipated radiation source tothe surface layer. Typically, the predetermined distance threshold isapproximately 7 mm or less from the balloon to the surface layer,however, this distance threshold might vary somewhat based on specificusage. If no shielding is deemed warranted, the process continues atstep 485. However, if shielding is deemed warranted, at step 470,shielding material may be applied to the applicator. At step 475,magnetic fields may be applied, typically based on results of modelingfor field strength and magnetic field orientation. At step 480, theshielding material alignment and/or sizing in the applicator may beverified via imaging or dosimetric studies. At step 485, a radiationdose may be applied per a treatment plan. At step 490, the dosage may beverified (e.g., by measurement) and treatment parameters modified toachieve optimization of the dose distribution. This may include alteringthe magnetic field to vary the shielding effectiveness (typically byvarying the spatial distribution of the magnetic material) and/oraltering the position of the radiation source. This optimization may bedone in real-time. At step 495, the process ends.

FIG. 5 is a flow diagram showing steps for modeling various factorsrelated to the optimizing dose distribution, according to principles ofthe invention, starting at step 500. FIG. 5 may also be a block diagramof the components needed to execute the steps thereof. For example, thecomponents of FIG. 5 may be executable software executing on a suitablecomputer platform or stored in a computer readable medium such as amemory or disk. The components of FIG. 5 may also include modelingsoftware.

At step 505, imaging projection data studies may be performed, perhapsseparating contributions from metal and non-metal objects. This mayinclude taking an image of the body part (e.g., a breast), perhaps usingComputed Tomography (CT) or another suitable imaging modality, to verifydistances between the surface of the IB applicator balloon and the bodypart surface (step 510). At step 515, parameters for skin-to-balloonspacing and specification of skin dose limits may be established. Atstep 520, analytic modeling of the amount of shielding material may beproduced. At step 525, analytic modeling for the magnetic fieldconfiguration may be established. This modeling may produce parametersincluding at least any one of: location of a magnet source; strength ofthe magnet source (and effective magnetic fields); and a shape of themagnetic field.

At step 530, an analytic model may be calculated using parameters fromsteps 515, step 520 and/or step 525 for determining a 3-D dosedistribution. At step 535, the dose calculation may be optimized basedon treatment goals, or other factors. At step 540, the dose distributionfor the shielding applicator may be optimized to achieve an adequatedose distribution in the treatment volume with the presence of theshielding materials. This dose calculation may be performed in real-timeand may provide a 3-D dose distribution in the treatment volume. Ifnecessary, the treatment plan may be modified based on, for example,skin surface dose measurement results. In some instances, the balloonsize may be adjusted by altering the amount of fluid in the balloon.This adjustment may also aid in placement of the balloon or shape of themagnetic shielding materials. At step 545, the process ends.

Outcomes

The improvements provided by the system and methods of the invention hasgood potential for national and international application, consideringthat currently more patients are choosing APBI over more conventionaltherapies, and even more patients and medical personnel will be able totake advantage of radiation therapy using the IB technology according toprinciples of the invention.

Various features provided by the invention aids in reducing risk fromlarge radiation exposure to the skin and other anatomical organs duringthe IB procedure, for example for patients with less than 7 mm skinspacing. The reduction in skin's radiation exposure may in additionreduce the risk of skin reactions (such as radiation recall dermatitis)for patients also undergoing chemotherapy.

Findings using Monte Carlo simulations of the shielded intracavitarydose-delivery with MammoSite provide confidence that treatments can becarried out practically and successfully. IB employing the methods orsystem of the invention is more effective in maintaining high localcontrol rates. Minimizing negative side effects is a significantbenefit. The system and methods of the invention are also relativelysimple to understand and use. Moreover, the methods and system of theinvention may also be used in treating appropriate body parts that mightbenefit from thin layer shielding.

Various modifications and variations of the described methods andsystems of the invention will be apparent to those skilled in the artwithout departing from the scope and spirit of the invention. Althoughthe invention has been described in connection with specific preferredembodiments, it should be understood that the invention as claimedshould not be unduly limited to such specific embodiments. Indeed,various modifications of the described modes for carrying out theinvention which are obvious to those skilled in the art are intended tobe within the scope of the following claims.

What is claimed is:
 1. A system for radiation treatment, comprising: anapplicator having a flexible containment portion configured to receive aradiation source and unformed radiation shielding material; a deviceconfigured to cause formation of a radiation shield by generating amagnetic field to rearrange the unformed shielding material to becomespatially oriented within the flexible containment portion according toa desired spatial orientation; and at least one computer based componentthat is configured to determine a necessary amount of the shieldingmaterial for limiting the dose to tissue not under radiation treatment,wherein the formed radiation shield is configured to block radiationemitted by the radiation source to protect a tissue area not underradiation treatment.
 2. The system of claim 1, further comprising: acomponent to determine magnetic parameters for producing the magneticfield to create the radiation shield.
 3. The system of claim 1, whereinthe flexible containment portion comprises a balloon portion of theapplicator.
 4. The system of claim 1, wherein the shielding materialcomprises any one of: a gold-iron alloy, iron powder, a magneticallysusceptible steel alloy, and iron oxide microparticles.
 5. The system ofclaim 1, wherein the shape of the radiation shield is alterable byaltering an amount of fluid in the flexible containment portion.
 6. Thesystem of claim 1, further comprising: a computer executable componentfor modeling at least one of: an appropriate amount of shieldingmaterial for use as the radiation shield, a location of a magneticsource to produce the magnetic field, a strength of the magnetic sourceand a shape of the magnetic field.
 7. The system of claim 1, wherein theformed radiation shield is formed along a section of a surface of theflexible containment portion while another section of the same surfaceremains unshielded.
 8. The system of claim 1, wherein the device isconfigured to alter the magnetic field to vary shielding effectivenessof the radiation shield.
 9. The system of claim 1, further comprising: acomputer executable component that establishes one or more parametersfor skin to the flexible containment portion spacing and skin doselimits.
 10. The system of claim 9, further comprising: a computerexecutable component that calculates an analytic model based on theestablished one or more parameters to determine a 3-D dose distributionfor a treatment plan.
 11. The system of claim 10, further comprising: acomputer based component that optimizes the 3-D dose distribution toachieve a dose distribution in a volume being treated with the presenceof the radiation shield.